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Mebendazole in Newly Diagnosed High-Grade Glioma Patients Receiving Temozolomide (Mebendazole)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01729260
Recruitment Status : Completed
First Posted : November 20, 2012
Last Update Posted : May 7, 2021
Accelerate Brain Cancer Cure
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
The purpose of this study is to find the highest dose of mebendazole (MBZ) that can be safely given to people with malignant brain tumors in combination with the current standard of care (temozolomide) without causing severe side effects. We also want to find out if MBZ can slow the growth of the brain tumor. The study doctors have found that MBZ is effective against malignant brain tumors in the laboratory and animal models of brain tumors.

Condition or disease Intervention/treatment Phase
Newly Diagnosed High-Grade Glioma Drug: Mebendazole Phase 1

Detailed Description:

Glioblastoma (GBM) is the most common and aggressive brain cancer, and despite significant advances in treatment the majority of patients die within two years of diagnosis. During routine animal studies we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used for pinworms, prevented tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the drug having the best results in preclinical testing 1. In GBM cell lines, mebendazole displayed cytotoxicity with IC50s ranging from 0.1-0.3 μM. Mebendazole disrupted microtubule formation in GBM cells and it's in vitro activity was correlated with reduced tubulin polymerization. In two orthotopic mouse glioma models, one syngeneic and one xenograft, mebendazole significantly extended average survival up to 63% compared to untreated controls 1.

Mebendazole is an FDA approved antiparasitic agent with a well-established side effect and safety record and was effective in our animal models in dosing schedules that are documented as safe in humans. Therefore, mebendazole is a possible anti-cancer therapeutic with pre-clinical safety and efficacy and provides a promising opportunity for a clinical trial in patients with malignant gliomas.

In addition, a recently published case report case report from the University of Michigan documented successful long term control in metastatic adrenocortical adenocarcinoma using mebendazole 2. Mebendazole was well tolerated at 200 mg/day and used as the sole treatment after the patient failed other chemotherapies.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Mebendazole in Newly Diagnosed High-Grade Glioma Patients Receiving Temozolomide
Actual Study Start Date : April 4, 2013
Actual Primary Completion Date : September 2016
Actual Study Completion Date : April 16, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Mebendazole
All study participants will receive study drug; Mebendazole.
Drug: Mebendazole
The mebendazole will be given by mouth three times every day on a 28 day cycle. it's in the form of 500 mg chewable tablets, to be taken with meals.
Other Name: Brand name: Vermox

Primary Outcome Measures :
  1. maximum tolerated dose (MTD) of mebendazole [ Time Frame: 8 months ]
    To determine the maximum tolerated dose (MTD) of mebendazole in combination with temozolomide (TMZ) given after surgery and the standard radiation and TMZ treatment in patients with newly diagnosed malignant gliomas.

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 10 years ]
    Overall survival in years.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have histologically confirmed newly diagnosed high-grade glioma(WHO Grade III or IV)
  2. Age ≥18 years
  3. Karnofsky Performance Score (KPS) ≥ 60%
  4. Life expectancy greater than 12 weeks
  5. Patients must have adequate organ and marrow function
  6. Completed >80% of the prescribed radiation therapy and concurrent temozolomide according to the Stupp regimen without grade 3 or 4 hematologic toxicity
  7. Patients may have received Gliadel during surgery
  8. Ability to swallow pills and keep medication record
  9. women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation.
  10. Ability to understand and willingness to sign a written informed consent document
  11. Be able to comply with treatment plan, study procedures and follow-up examinations

Exclusion Criteria:

  1. Patients must not have received prior therapy other than standard chemoradiation according to Stupp et al and Gliadel.
  2. Patients may not be receiving any other investigational agents while on study
  3. Patients who have known allergy to mebendazole or benzimidazole
  4. Patients who have previously had a severe side effect, such as agranulocytosis and neutropenia, in conjunction with previous mebendazole or benzimidazole class drug for a parasitic infection
  5. Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting mebendazole therapy
  6. Patients who have taken any benzimidazole (ABZ, flubendazole, thiabendazole, fenbendazole, triclabendazole, etc.) within the last 3 months
  7. Patients who are taking any anti-convulsant medication that interferes with the cytochrome P450 pathway (e.g. phenytoin, phenobarbital, carbamazepine, etc.)
  8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic hepatitis, acute hepatitis, or psychiatric illness/social situation that would limit compliance with study requirements
  9. Pregnant women are excluded
  10. Patients with human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive; or with a history of chronic active hepatitis or cirrhosis
  11. Patients with a history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product administration or may interfere with the interpretation of the results
  12. Patients who are not available for follow-up assessments or unable to comply with study requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01729260

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United States, Maryland
The Johs Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Accelerate Brain Cancer Cure
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Principal Investigator: Gary Gallia, MD Johns Hopkins University School of Medicine, Department of Neurosurgery
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT01729260    
Other Study ID Numbers: J1194
NA_00049848 ( Other Identifier: JHMIRB )
First Posted: November 20, 2012    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Piperazine citrate
DMP 777
Antinematodal Agents
Antiparasitic Agents
Anti-Infective Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors